Transcriptional response to interferon beta-1a treatment in patients with secondary progressive multiple sclerosis.

Abstract

BACKGROUND:

Interferon (IFN) beta-1a is an approved treatment for relapsing remitting multiple sclerosis (RRMS) and has been examined for use in secondary progressive multiple sclerosis (SPMS). However, no information regarding blood transcriptional changes induced by IFN treatment in SPMS patients is available. Our aim was to identify a subgroup of SPMS patients presenting a gene expression signature similar to that of RRMS patients who are clinical responders to IFN treatment.

METHODS:

SPMS patients (n = 50, 20 IFN treated and 30 untreated) were classified using unsupervised hierarchical clustering according to IFN inducible gene expression profile identified in RRMS clinical responders to treatment. IFN inducible gene expression profile was determined by finding differentially expressed genes (DEGs) between IFN treated (n = 10) and untreated (n = 25) RRMS patients. Validation was performed on an additional independent group of 27 SPMS IFN treated patients by qRT-PCR.

RESULTS:

One hundred and four DEGs, enriched by IFN signaling pathway (p = 7.4E-08), were identified in IFN treated RRMS patients. Classification of SPMS patients based on these DEGs yielded two patient groups: (1) IFN transcriptional responders (n = 12, 60% of SPMS treated patients) showing gene-expression profile similar to IFN treated RRMS patients; (2) IFN transcriptional non-responders (n = 8) showing expression profile similar to untreated patients. IFN transcriptional responders were characterized by a more active disease, as defined by higher EDSS progression and annual relapse rate.

CONCLUSION:

Within the IFN treated SPMS population, 60% of patients have a transcriptional response to IFN which is similar to that of RRMS patients who are IFN responders to treatment.

• Authors: Michael Gurevich, Gadi Miron, Rina Zilkha Falb, David Magalashvili, Mark Dolev, Yael Stern, Anat Achiron
• Journal: BMC neurology (BMC Neurol) Vol. 15 Pg. 240 (Nov 21 2015) ISSN: 1471-2377 [Electronic] England
• PMID: 26589141 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Interferon beta-1a

Topics

• Adjuvants, Immunologic (therapeutic use)
• Adult
• Disease Progression
• Female
• Gene Expression Profiling
• Humans
• Interferon beta-1a (therapeutic use)
• Male
• Middle Aged
• Multiple Sclerosis, Chronic Progressive (drug therapy, genetics)
• Retrospective Studies
• Transcription, Genetic